Role of N - Methy lo lpentamethy lme lamine in the Metabol ic Activation of

Hexamethylmelamine (HMM) is metabolized by rat hepatic microsomal preparat ions to reactive species which covalent ly bind to microsomal protein and to calf thymus DNA added to microsomal incubation mixtures. Covalent binding to macromolecules is dependent on the presence of molecular oxygen and reduced nicot inamide adenine dinucleot ide phosphate and is catalyzed by cytochrome P-450 monooxygenases. Reduced nicotinamide adenine d inucleot ide-dependent covalent binding of [methylJ4C]HMM to microsomal protein is greater than that of [ r ing j4C]HMM. Reduced nicot inamide adenine dinucleot ide phosphate-dependent covalent binding of [ r ing j4C]HMM and [methyl-14C]HMM to calf thymus DNA added to microsomal incubation mixtures are approximately equal. The [ring-14C]labeled carbinolamine intermediate in HMM demethylat ion, Nmethylolpentamethylmelamine, covalent ly binds to microsomal protein and, to a much greater extent, to calf thymus DNA.